tbuckley/cabot-search huggingface dataset:
Diet and Exercise and Knee Pain in Patients With Osteoarthritis and Overweight or Obesity
Authors: Danli Cui, Yiting Lei
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Diet and Exercise and Knee Pain in Patients With Osteoarthritis and Overweight or Obesity—Reply
Authors: Stephen P. Messier, Daniel P. Beavers
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Dynamics of Sequence and Structural Cell-Free DNA Landscapes in Small-Cell Lung Cancer
Authors: Lavanya Sivapalan, Wade T. Iams, Zineb Belcaid, Susan C. Scott, Noushin Niknafs, Archana Balan, James R. White, Prasad Kopparapu, Christopher Cann, Blair V. Landon, Gavin Pereira, Victor E. Velculescu, Christine L. Hann, Christine M. Lovly, Valsamo Anagnostou
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Patients with small-cell lung cancer (SCLC) have an exceptionally poor prognosis, calling for improved real-time noninvasive biomarkers of therapeutic response. Experimental Design: We performed targeted error-correction sequencing on 171 serial plasmas and matched white blood cell (WBC) DNA from 33 patients with metastatic SCLC who received treatment with chemotherapy (n = 16) or immunotherapy-containing (n = 17) regimens. Tumor-derived sequence alterations and plasma aneuploidy were evaluated serially and combined to assess changes in total cell-free tumor load (cfTL). Longitudinal dynamic changes in cfTL were monitored to determine circulating cell-free tumor DNA (ctDNA) molecular response during therapy. Results: Combined tiered analyses of tumor-derived sequence alterations and plasma aneuploidy allowed for the assessment of ctDNA molecular response in all patients. Patients classified as molecular responders (n = 9) displayed sustained elimination of cfTL to undetectable levels. For 14 patients, we observed initial molecular responses, followed by ctDNA recrudescence. A subset of patients (n = 10) displayed a clear pattern of molecular progression, with persistence of cfTL across all time points. Molecular responses captured the therapeutic effect and long-term clinical outcomes in a more accurate and rapid manner compared with radiographic imaging. Patients with sustained molecular responses had longer overall (log-rank P = 0.0006) and progression-free (log-rank P &amp;lt; 0.0001) survival, with molecular responses detected on average 4 weeks earlier than imaging. Conclusions: ctDNA analyses provide a precise approach for the assessment of early on-therapy molecular responses and have important implications for the management of patients with SCLC, including the development of improved strategies for real-time tumor burden monitoring. See related commentary by Pellini and Chaudhuri, p. 2176
Analysis of Hospital Operating Margins and Provision of Safety Net Services
Authors: Lukas K. Gaffney, Kenneth A. Michelson
Journal: JAMA Network Open (2023)

Importance Safety net hospitals (SNH) provide many community services. The cost of providing these services is unknown. Objective To determine what safety net criteria are associated with differences in hospital operating margin. Design, Setting, and Participants This cross-sectional study of US acute care hospitals from 2017 to 2019 included eligible hospitals identified from US Centers for Medicare &amp;amp;amp; Medicaid Services Cost Reports. Exposures Five domains of SNH: undercompensated care measured using the Disproportionate Share Hospital index, uncompensated care, essential community services, neighborhood disadvantage, and sole community hospital and critical access hospital status. Each was categorized as a quintile or binary response. Covariates included hospital ownership, size, teaching status, census region, urbanicity, and wage index. Main Outcomes and Measures Operating margin and its association with each safety net criterion was determined using linear regression adjusting for all safety net criteria and covariates. Results A total of 4219 hospitals were analyzed, of which 3329 hospitals (78.9%) satisfied at least 1 safety net criterion; 23 hospitals (0.5%) met 4 or all 5 criteria. Among safety net criteria, the highest quintile of undercompensated care (−6.2 percentage point difference compared with lowest quintile; 95% CI, −8.2 to −4.2 percentage points), uncompensated care (−3.4 percentage points; 95% CI, −5.1 to −1.6 percentage points), and neighborhood disadvantage (−3.9 percentage points; 95% CI, −5.7 to −2.1 percentage points) were each associated with a lower operating margin. No association with operating margin was found between critical access or sole community hospital status (0.9 percentage points; 95% CI, −0.8 to 2.7 percentage points) or the highest vs lowest quintile of essential services (0.8 percentage points; 95% CI, −1.2 to 2.7 percentage points). Among essential services, burn, inpatient psychiatry, and primary care services were associated with lower operating margin, while others were either not associated or showed positive association. Fall-off in operating margin by level of uncompensated care was most severe in the highest percentiles of uncompensated care, with the most marked declines among those with the lowest operating margin. Conclusions and Relevance In this cross-sectional study of SNH, hospitals in the highest quintiles of undercompensated care, uncompensated care, and neighborhood disadvantage were more financially vulnerable than those not in the top quintile, especially when they met numerous of these criteria. Ensuring targeting of financial support to these hospitals could improve their financial stability.
The USPSTF I Statement on Skin Cancer Screening—Not a Disappointment but an Opportunity
Authors: Adewole S. Adamson
Journal: JAMA Dermatology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Thematic reviews: The future of hepatology
Authors: Harmeet Malhi, Vijay Shah, Gregory J. Gores
Journal: Hepatology (2023)

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN Correspondence Gregory J. Gores, MD, Professor of Medicine and Physiology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, Tel.: 507-284-0686; Fax: 507-284-0762. Email: [email protected]
Nanocomplexes of Biodegradable Anticancer Macromolecules: Prolonged Plasma Half‐Life, Reduced Toxicity, and Increased Tumor Targeting
Authors: Jiayu Leong, Joyce Tay, Shengcai Yang, Chuan Yang, Eddy Wei Ping Tan, Yanming Wang, Bing Qian Tan, Sherwin Hor, Yau Hong Chua, Jeremy Pang Kern Tan, Qingfeng Chen, James L. Hedrick, Yi Yan Yang
Journal: Advanced Healthcare Materials (2023)

Abstract Anticancer drug resistance is a large contributing factor to the global mortality rate of cancer patients. Anticancer macromolecules such as polymers have been recently reported to overcome this issue. Anticancer macromolecules have unselective toxicity because they are highly positively charged. Herein, an anionic biodegradable polycarbonate carrier is synthesized and utilized to form nanocomplexes with an anticancer polycarbonate via self‐assembly to neutralize its positive charges. Biotin is conjugated to the anionic carrier and serves as cancer cell‐targeting moiety. The nanoparticles have sizes of &lt; 130 nm with anticancer polymer loading levels of 38–49%. Unlike the small molecular anticancer drug doxorubicin, the nanocomplexes effectively inhibit the growth of both drug‐susceptible MCF7 and drug‐resistant MCF7/ADR human breast cancer cell lines with low half maximal inhibitory concentration (IC 50 ). The nanocomplexes increase the anticancer polymer's in vivo half‐life from 1 to 6–8 h, and rapidly kill BT474 human breast cancer cells primarily via an apoptotic mechanism. The nanocomplexes significantly increase the median lethal dose (LD 50 ) and reduce the injection site toxicity of the anticancer polymer. They suppress tumor growth by 32–56% without causing any damage to the liver and kidneys. These nanocomplexes may potentially be used for cancer treatment to overcome drug resistance.
Temperature regulates Rab3a and mast cell‐derived exosomal <scp>FcεRI</scp> to inhibit mast cell activation
Authors: Wenjing Liao, Gui Chen, Lijuan Song, Meiqian Xu, Hao Li, Yiyan Wang, Xiaofen Wang, Jinfeng Ye, Mei Ren, Xiaoxuan Kuang, Yaqiang Tang, Saixuan Yang, Xiaoping Ning, Jianlei Xie, Zhaowei Yang, Xiaowen Zhang
Journal: Allergy (2023)

Data S1 Figure S1 Figure S2 Figure S3 Tables S1–S2 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Kinome Reprogramming Is a Targetable Vulnerability in ESR1 Fusion-Driven Breast Cancer
Authors: Xuxu Gou, Beom-Jun Kim, Meenakshi Anurag, Jonathan T. Lei, Meggie N. Young, Matthew V. Holt, Diana Fandino, Craig T. Vollert, Purba Singh, Mohammad A. Alzubi, Anna Malovannaya, Lacey E. Dobrolecki, Michael T. Lewis, Shunqiang Li, Charles E. Foulds, Matthew J. Ellis
Journal: Cancer Research (2023)

Abstract Transcriptionally active ESR1 fusions (ESR1-TAF) are a potent cause of breast cancer endocrine therapy (ET) resistance. ESR1-TAFs are not directly druggable because the C-terminal estrogen/anti-estrogen–binding domain is replaced with translocated in-frame partner gene sequences that confer constitutive transactivation. To discover alternative treatments, a mass spectrometry (MS)–based kinase inhibitor pulldown assay (KIPA) was deployed to identify druggable kinases that are upregulated by diverse ESR1-TAFs. Subsequent explorations of drug sensitivity validated RET kinase as a common therapeutic vulnerability despite remarkable ESR1-TAF C-terminal sequence and structural diversity. Organoids and xenografts from a pan-ET–resistant patient-derived xenograft model that harbors the ESR1-e6&amp;gt;YAP1 TAF were concordantly inhibited by the selective RET inhibitor pralsetinib to a similar extent as the CDK4/6 inhibitor palbociclib. Together, these findings provide preclinical rationale for clinical evaluation of RET inhibition for the treatment of ESR1-TAF–driven ET-resistant breast cancer. Significance: Kinome analysis of ESR1 translocated and mutated breast tumors using drug bead-based mass spectrometry followed by drug-sensitivity studies nominates RET as a therapeutic target. See related commentary by Wu and Subbiah, p. 3159
Prescription Stimulant Medical and Nonmedical Use Among US Secondary School Students, 2005 to 2020
Authors: Sean Esteban McCabe, John E. Schulenberg, Timothy E. Wilens, Ty S. Schepis, Vita V. McCabe, Philip T. Veliz
Journal: JAMA Network Open (2023)

Importance Recent information on the prevalence of prescription stimulant therapy for attention-deficit/hyperactivity disorder (ADHD) and nonmedical use of prescription stimulants (NUPS) at the school-level among US secondary school students is limited. Objective To investigate the school-level prevalence of and association between stimulant therapy for ADHD and NUPS among US secondary school students. Design, Setting, and Participants This cross-sectional study used survey data collected between 2005 and 2020 as part of the Monitoring the Future study (data collected annually via self-administered survey in schools from independent cohorts). Participants were from a nationally representative sample of 3284 US secondary schools. The mean (SD) response rates were 89.5% (1.3%) for 8th-grade students, 87.4% (1.1%) for 10th-grade students, and 81.5% (1.8%) for 12th-grade students. Statistical analysis was performed from July to September 2022. Main Outcome and Measure Past-year NUPS. Results The 3284 schools contained 231 141 US 8th-, 10th-, and 12th-grade students (111 864 [50.8%, weighted] female; 27 234 [11.8%, weighted] Black, 37 400 [16.2%, weighted] Hispanic, 122 661 [53.1%, weighted] White, 43 846 [19.0%, weighted] other race and ethnicity). Across US secondary schools, the past-year prevalence of NUPS ranged from 0% to more than 25%. The adjusted odds of an individual engaging in past-year NUPS were higher at secondary schools with higher proportions of students who reported stimulant therapy for ADHD, after controlling for other individual-level and school-level covariates. Students attending schools with the highest rates of prescription stimulant therapy for ADHD had approximately 36% increased odds of past-year NUPS compared with students attending schools with no medical use of prescription stimulants (adjusted odds ratio, 1.36; 95% CI, 1.20-1.55). Other significant school-level risk factors included schools in more recent cohorts (2015-2020), schools with higher proportions of parents with higher levels of education, schools located in non-Northeastern regions, schools located in suburban areas, schools with higher proportion of White students, and schools with medium levels of binge drinking. Conclusions and Relevance In this cross-sectional study of US secondary schools, the prevalence of past-year NUPS varied widely, highlighting the need for schools to assess their own students rather than relying solely on regional, state, or national results. The study offered new evidence of an association between a greater proportion of the student body that uses stimulant therapy and a greater risk for NUPS in schools. The association between greater school-level stimulant therapy for ADHD and other school-level risk factors suggests valuable targets for monitoring, risk-reduction strategies, and preventive efforts to reduce NUPS.
Patterns of Oncogene Coexpression at Single-Cell Resolution Influence Survival in Lymphoma
Authors: Michal Marek Hoppe, Patrick Jaynes, Fan Shuangyi, Yanfen Peng, Shruti Sridhar, Phuong Mai Hoang, Clementine Xin Liu, Sanjay De Mel, Limei Poon, Esther Hian Li Chan, Joanne Lee, Choon Kiat Ong, Tiffany Tang, Soon Thye Lim, Chandramouli Nagarajan, Nicholas F. Grigoropoulos, Soo-Yong Tan, Susan Swee-Shan Hue, Sheng-Tsung Chang, Shih-Sung Chuang, Shaoying Li, Joseph D. Khoury, Hyungwon Choi, Carl Harris, Alessia Bottos, Laura J. Gay, Hendrik F.P. Runge, Ilias Moutsopoulos, Irina Mohorianu, Daniel J. Hodson, Pedro Farinha, Anja Mottok, David W. Scott, Jason J. Pitt, Jinmiao Chen, Gayatri Kumar, Kasthuri Kannan, Wee Joo Chng, Yen Lin Chee, Siok-Bian Ng, Claudio Tripodo, Anand D. Jeyasekharan
Journal: Cancer Discovery (2023)

Cancers often overexpress multiple clinically relevant oncogenes, but it is not known if combinations of oncogenes in cellular subpopulations within a cancer influence clinical outcomes. Using quantitative multispectral imaging of the prognostically relevant oncogenes MYC, BCL2, and BCL6 in diffuse large B-cell lymphoma (DLBCL), we show that the percentage of cells with a unique combination MYC+BCL2+BCL6- (M+2+6-) consistently predicts survival across four independent cohorts (n = 449), an effect not observed with other combinations including M+2+6+. We show that the M+2+6- percentage can be mathematically derived from quantitative measurements of the individual oncogenes and correlates with survival in IHC (n = 316) and gene expression (n = 2,521) datasets. Comparative bulk/single-cell transcriptomic analyses of DLBCL samples and MYC/BCL2/BCL6-transformed primary B cells identify molecular features, including cyclin D2 and PI3K/AKT as candidate regulators of M+2+6- unfavorable biology. Similar analyses evaluating oncogenic combinations at single-cell resolution in other cancers may facilitate an understanding of cancer evolution and therapy resistance. Using single-cell-resolved multiplexed imaging, we show that selected subpopulations of cells expressing specific combinations of oncogenes influence clinical outcomes in lymphoma. We describe a probabilistic metric for the estimation of cellular oncogenic coexpression from IHC or bulk transcriptomes, with possible implications for prognostication and therapeutic target discovery in cancer. This article is highlighted in the In This Issue feature, p. 1027.
The Polyamine–Hypusine Circuit Controls an Oncogenic Translational Program Essential for Malignant Conversion in MYC-Driven Lymphoma
Authors: Shima Nakanishi, Jiannong Li, Anders E. Berglund, Youngchul Kim, Yonghong Zhang, Ling Zhang, Chunying Yang, Jinming Song, Raghavendra G. Mirmira, John L. Cleveland
Journal: Blood Cancer Discovery (2023)

Abstract The MYC oncoprotein is activated in a broad spectrum of human malignancies and transcriptionally reprograms the genome to drive cancer cell growth. Given this, it is unclear if targeting a single effector of MYC will have therapeutic benefit. MYC activates the polyamine–hypusine circuit, which posttranslationally modifies the eukaryotic translation factor eIF5A. The roles of this circuit in cancer are unclear. Here we report essential intrinsic roles for hypusinated eIF5A in the development and maintenance of MYC-driven lymphoma, where the loss of eIF5A hypusination abolishes malignant transformation of MYC-overexpressing B cells. Mechanistically, integrating RNA sequencing, ribosome sequencing, and proteomic analyses revealed that efficient translation of select targets is dependent upon eIF5A hypusination, including regulators of G1–S phase cell-cycle progression and DNA replication. This circuit thus controls MYC's proliferative response, and it is also activated across multiple malignancies. These findings suggest the hypusine circuit as a therapeutic target for several human tumor types. Significance: Elevated EIF5A and the polyamine–hypusine circuit are manifest in many malignancies, including MYC-driven tumors, and eIF5A hypusination is necessary for MYC proliferative signaling. Not­ably, this circuit controls an oncogenic translational program essential for the development and maintenance of MYC-driven lymphoma, supporting this axis as a target for cancer prevention and treatment. See related commentary by Wilson and Klein, p. 248. This article is highlighted in the In This Issue feature, p. 247
Adjuvant gemcitabine plus cisplatin versus capecitabine in node-positive extrahepatic cholangiocarcinoma: the STAMP randomized trial
Authors: Hyehyun Jeong, Kyu-pyo Kim, Jae Ho Jeong, Dae Wook Hwang, Jae Hoon Lee, Ki-Hun Kim, Deok-Bog Moon, Myung Ah Lee, Se Jun Park, Hong Jae Chon, Jin-hong Park, Ji Sung Lee, Baek-Yeol Ryoo, Changhoon Yoo
Journal: Hepatology (2023)

The effectiveness of gemcitabine-based adjuvant chemotherapy is unclear in cholangiocarcinoma. We investigated the role of adjuvant gemcitabine plus cisplatin (GemCis) in a homogeneous group of high-risk patients with resected, lymph node-positive extrahepatic cholangiocarcinoma.Adenocarcinoma of perihilar or distal bile duct with regional lymph node metastasis who underwent curative-intent surgery (R0/R1) was eligible. Patients were randomized to receive GemCis (gemcitabine 1000 mg/m2, cisplatin 25 mg/m2 on days 1 and 8) or capecitabine (1250 mg/m2 twice daily on days 1-14) every 3 weeks for 8 cycles. Primary endpoint was disease-free survival. Secondary endpoints were overall survival and safety. All p values are 1 sided and were considered significant if <0.1. Between July 2017 and November 2020, 101 patients (50 in the GemCis and 51 in the capecitabine group) were included in the intention-to-treat population. Perihilar and distal bile ducts were the primary sites in 45 (44.6%) and 56 (55.4%) patients, respectively, and 32 (31.7%) had R1 resections. Median (1-sided 90% CI) follow-up duration was 33.4 (30.5-35.8) months. In the GemCis and capecitabine group, 2-year disease-free survival rates were 38.5% (29.5%-47.4%) and 25.1% (17.4%-33.5%) [HR=0.96 (CI, 0.71-1.30), p=0.430], and median overall survival was 35.7 months (29.5-not estimated) and 35.7 months (30.9-not estimated) [HR=1.08 (CI, 0.71-1.64), 1-sided p=0.404], respectively. Grade 3-4 adverse events occurred in 42 (84.0%) and 8 patients (16.0%) in the GemCis and capecitabine groups, respectively. No treatment-related deaths were reported.In resected lymph node-positive extrahepatic cholangiocarcinoma, adjuvant GemCis did not improve survival outcomes compared with capecitabine.
COVID-19 and Incident Diabetes—Recovery Is Not So Sweet After All
Authors: Pamela B. Davis, Rong Xu
Journal: JAMA Network Open (2023)

Zaeema Naveed, MBBS, PhD; Héctor A. Velásquez García, MD, PhD; Stanley Wong, MS; James Wilton, MPH; Geoffrey McKee, MD; Bushra Mahmood, PhD; Mawuena Binka, PhD; Drona Rasali, PhD; Naveed Z. Janjua, MBBS, DrPH
Diet and Exercise and Knee Pain in Patients With Osteoarthritis and Overweight or Obesity
Authors: Tianxiang Fan, Muhui Zeng, Zhaohua Zhu
Journal: JAMA (2023)

To the Editor We would like to draw attention to 3 concerns about the recent clinical trial evaluating the effect of diet and exercise on knee pain in patients with knee osteoarthritis (OA) and overweight or obesity.1